U.S. Pat. Nos. 6,865,416 and 6,347,247 to Dev et al., which are incorporated herein by reference, describe methods for inducing or increasing the vasodilation of a vessel, or the flow of blood therethrough, including applying an electrical impulse to the vessel. According to the inventors in the '416 and 247 applications, the induction or increase of vessel vasodilation by an electrical impulse appears to result either from a direct effect caused by the electrical current applied to the vessel, or an indirect effect resulting from the release or stimulation of factors that promote vasodilation, such as the release of endothelium derived relaxation factors (EDRF) currently identified as nitric oxide (NO) or other vasodilating substances triggered by the electrical pulses applied to the cells of the vessel. In an embodiment, a double-balloon catheter system incorporating electroporation technology is used to apply the electrical impulse endoluminally.
US Patent Application Publication 2003/0204206 to Padua et al., which is incorporated herein by reference, describes techniques for regulating delivery of therapeutic proteins and nucleic acids. The techniques include using a genetically-engineered electrically-responsive promoter operably linked to a therapeutic gene sequence, wherein expression of said sequence is controlled by an electrical pulse generator. In an embodiment, the pulse generator is able to deliver charge balanced electrical pulses at rate of about 10 to 100 Hz, preferably about 30 to 80 Hz, and more preferably about 50 to 60 Hz. In an embodiment, an implantable system uses an RF signal to communicate and generate an electrical current in a coiled stent. In an embodiment, an electric field is applied to engineered cells grown on a scaffolding, using either a conductive matrix having parallel electrodes, or a conductive stent matrix.
U.S. Pat. No. 6,845,267 to Harrison et al., which is incorporated herein by reference, describes an implantable control unit adapted to apply stimulating drugs and/or electrical pulses to predetermined areas affecting circulatory perfusion. In an embodiment, the implantable control unit applies electrical stimulation directly to smooth muscle to modulate its contractile state. The '267 patent states that relatively low frequency electrical stimulation ([sic] than about 50-100 Hz) tends to excite smooth muscle and lead to contraction, and relatively high frequency electrical stimulation tends to relax smooth muscle and lead to dilation. In an embodiment, electrical and/or drug stimulation is applied to autonomic sites responsible for innervation of the coronary arteries, and/or directly to the smooth muscle surrounding these arteries, in order to dilate the coronary arteries and provide relief from cardiac ischemia. For some applications, the implantable control unit includes an electrical coil or other means of receiving energy and/or information inside the package, which receives power and/or data by inductive or radio-frequency (RF) coupling to a transmitting coil placed outside the body. For some applications, the control unit communicates with other implanted stimulators, other implanted devices, and/or devices external to a patient's body, e.g., via an RF link, an ultrasonic link, or an optical link.
U.S. Pat. No. 6,871,092 to Piccone, which is incorporated herein by reference, describes apparatus for the treatment of vascular, muscle and/or tendon disorders, for increasing the production of Vascular Endothelial Growth Factor (VEGF), for anti-inflammatory treatment, and/or for the activation of microcirculation. The apparatus generates and applies electrical pulses through the epidermis of a subject. The pulses are described as inducing a biochemical response which not only eliminates inflammation from the part of the body treated and reduces or eliminates pain, but also has a rapid muscle-relaxant effect, and stimulates vasodilatation and VEGF production.
US Patent Application Publication 2004/0106954 to Whitehurst et al., which is incorporated herein by reference, describes techniques for treating congestive heart failure (CHF) by implanting of a discharge portion of a catheter and, optionally, an electrode on a lead, near tissue to be stimulated. Stimulation pulses, such as drug infusion pulses and optional electrical pulses, are supplied by a stimulator implanted remotely, and through the catheter or lead, which is tunneled subcutaneously between the stimulator and stimulation site. Stimulation sites include the coronary arteries, the aorta, the left ventricle, the left atrium, and/or the pulmonary veins, among other locations. For some applications, a stimulator includes electrical circuitry (including, for example, an inductive coil) for receiving data and/or power from outside the body by inductive, radio frequency (RF), or other electromagnetic coupling. For some applications, the stimulator communicates with other implanted stimulators, other implanted devices, and/or devices external to a patient's body via, e.g., an RF link, an ultrasonic link, a thermal link, and/or an optical link.
US Patent Application Publication 2006/0074453 to Kieval et al., which is incorporated herein by reference, describes a method for treating heart failure in a patient, including activating a baroreflex system of the patient with at least one baroreflex activation device and resynchronizing the patient's heart with a cardiac resynchronization device. Activating the baroreflex system and resynchronizing the heart may be performed simultaneously or sequentially, in various embodiments. A device for treating heart failure includes a baroreflex activation member coupled with a cardiac resynchronization member. The baroreflex activation member may comprise a wide variety of devices which utilize mechanical, electrical, thermal, chemical, biological, or other means to activate baroreceptors and/or other tissues. In many embodiments, particularly the mechanical activation embodiments, the baroreflex device indirectly activates one or more baroreceptors by stretching or otherwise deforming the vascular wall surrounding the baroreceptors.
US Patent Application Publication 2003/0060858 to Kieval et al., which is incorporated herein by reference, describes techniques for selectively and controllably reducing blood pressure, nervous system activity, and neurohormonal activity by activating baroreceptors. A baroreceptor activation device is positioned near a baroreceptor, for example a baroreceptor in the carotid sinus. A control system may be used to modulate the baroreceptor activation device. In some embodiments, the baroreceptor activation device takes the form of an intravascular deformable structure. The deformable structure device includes a coil, braid or other stent-like structure disposed in the vascular lumen. In other embodiments, the baroreceptor activation device takes the form of an extravascular deformable structure, which is disposed about the vascular wall, and therefore compresses, rather than expands, the vascular wall. The deformable structure device includes a coil, braid or other stent-like structure.
U.S. Pat. No. 6,086,527 to Talpade, which is incorporated herein by reference, describes a system for regulating blood flow to a portion of the vasculature, such as the renal system, in order to treat heart disease. A regulator maintains blood flow so as to control physiological feedback responses in order to relieve overload conditions on the heart.
US Patent Application Publication 2002/0103454 to Sackner et al., which is incorporated herein by reference, describes methods of medical treatment and diagnosis using mediators released by endothelial cells stimulated by external addition of pulses to the circulation. The external pulses produce circumferential shear stress in body fluid channels that subsequently stimulates the endothelial cells to produce mediators that become available for therapeutic and diagnostic purposes. The preferred means of adding external pulses is the mechanical inducement of periodic acceleration of the body or parts of the body by a reciprocating motion platform.
US Patent Application Publication 2005/0149130 to Libbus et al., which is incorporated herein by reference, describes a baroreflex stimulator including a pulse generator for providing a baroreflex stimulation signal through an electrode, and a modulator to modulate the baroreflex stimulation signal based on a circadian rhythm template. In some embodiments, the stimulator includes a sensor to sense automatic nervous system (ANS) activity. Such a sensor can be used to perform feedback in a closed loop control system. For example, various embodiments sense surrogate parameters, such as respiration and blood pressure, indicative of ANS activity.
The following patents and patent application publications, all of which are incorporated herein by reference, may be of interest:
U.S. Pat. No. 6,824,561 and US Patent Application Publication 2004/0039417 to Soykan et al.
U.S. Pat. No. 6,810,286 to Donovan et al.
U.S. Pat. No. 6,463,323 to Conrad-Vlasak et al.
U.S. Pat. No. 6,058,331 to King
U.S. Pat. No. 6,200,259 to March
US Patent Application Publication 2003/0036773 to Whitehurst et al.
European Patent Application Publication EP 0 109 935 A1 to Charmillot et al.
Levenberg S et al., in an articled entitled, “Endothelial cells derived from human embryonic stem cells,” Proc Natl Acad Sci USA 99(7):4391-6 (2002) Epub 2002 Mar. 26, which is incorporated herein by reference, describe the differentiation steps of human embryonic stem cells into endothelial cells forming vascular-like structures.